Small Molecule Tools to Study Cellular Target Engagement for the Intracellular Allosteric Binding Site of GPCRs

Huber M, Toy L, Schmidt M, Weikert D, Schiedel M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

DOI: 10.1002/chem.202202565

Abstract

A conserved intracellular allosteric binding site (IABS) has recently been identified at several G protein-coupled receptors (GPCRs). Ligands targeting the IABS, so-called intracellular allosteric antagonists, are highly promising compounds for pharmaceutical intervention and currently evaluated in several clinical trials. Beside co-crystal structures that laid the foundation for the structure-based development of intracellular allosteric GPCR antagonists, small molecule tools that enable an unambiguous identification and characterization of intracellular allosteric GPCR ligands are of utmost importance for drug discovery campaigns in this field. Herein, we discuss recent approaches that leverage cellular target engagement studies for the IABS and thus play a critical role in the evaluation of IABS-targeted ligands as potential therapeutic agents.

Authors with CRIS profile

Max Huber Lehrstuhl für Pharmazeutische Chemie Lara Toy Lehrstuhl für Pharmazeutische Chemie Maximilian Schmidt Lehrstuhl für Pharmazeutische Chemie Dorothée Weikert Lehrstuhl für Pharmazeutische Chemie Matthias Schiedel Lehrstuhl für Pharmazeutische Chemie

How to cite

APA:

Huber, M., Toy, L., Schmidt, M., Weikert, D., & Schiedel, M. (2022). Small Molecule Tools to Study Cellular Target Engagement for the Intracellular Allosteric Binding Site of GPCRs. Chemistry - A European Journal. https://dx.doi.org/10.1002/chem.202202565

MLA:

Huber, Max, et al. "Small Molecule Tools to Study Cellular Target Engagement for the Intracellular Allosteric Binding Site of GPCRs." Chemistry - A European Journal (2022).

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